Delayed speech and language development, and Dilated cardiomyopathy

High match ISOBUTYRYL-CoA DEHYDROGENASE DEFICIENCY

gene (11q25).

ISOBUTYRYL-CoA DEHYDROGENASE DEFICIENCY Is also known as ibd deficiency, acyl-coa dehydrogenase family, member 8, deficiency of, acad8 deficiency;isobutyric aciduria

• Autosomal recessive inheritance
• Seizures
• Global developmental delay
• Generalized hypotonia
• Muscular hypotonia

SOURCES: GARD MONDO ORPHANET OMIM SCTID MESH UMLS NCIT

High match MUSCULAR DYSTROPHY, LIMB-GIRDLE, TYPE 2E; LGMD2E

Autosomal recessive limb girdle muscular dystrophy type 2E (LGMD2E) is a subtype of autosomal recessive limb girdle muscular dystrophy characterized by a childhood to adolescent onset of progressive pelvic- and shoulder-girdle muscle weakness, particularly affecting the pelvic girdle (adductors and flexors of hip). Usually the knees are the earliest and most affected muscles. In advanced stages, involvement of the shoulder girdle (resulting in scapular winging) and the distal muscle groups are observed. Calf hypertrophy, cardiomyopathy, respiratory impairment, tendon contractures, scoliosis, and exercise-induced myoglobinuria may be observed.

MUSCULAR DYSTROPHY, LIMB-GIRDLE, TYPE 2E; LGMD2E Is also known as ;beta-sarcoglycanopathy; lgmd2e; limb-girdle muscular dystrophy due to beta-sarcoglycan deficiency

• Autosomal recessive inheritance
• Milia
• Myopathy
• Nevus
• Delayed speech and language development

SOURCES: MONDO SCTID DOID OMIM UMLS GARD ORPHANET

High match MUSCULAR DYSTROPHY, CONGENITAL, MEGACONIAL TYPE; MDCMC

This form of autosomal recessive congenital muscular dystrophy is characterized by early-onset muscle wasting and mental retardation. Some patients develop fatal cardiomyopathy. Muscle biopsy shows peculiar enlarged mitochondria that are prevalent toward the periphery of the fibers but are sparse in the center (summary by Mitsuhashi et al., 2011).

MUSCULAR DYSTROPHY, CONGENITAL, MEGACONIAL TYPE; MDCMC Is also known as muscular dystrophy, congenital, with mitochondrial structural abnormalities;congenital megaconial myopathy; congenital muscular dystrophy due to phosphatidylcholine biosynthesis defect; congenital muscular dystrophy with mitochondrial structural abnormalities

• Autosomal recessive inheritance
• Intellectual disability
• Seizures
• Global developmental delay
• Generalized hypotonia

SOURCES: MONDO DOID OMIM ORPHANET UMLS MESH GARD

High match MULTIPLE MITOCHONDRIAL DYSFUNCTIONS SYNDROME 2 WITH HYPERGLYCINEMIA; MMDS2

Multiple mitochondrial dysfunctions syndrome-2 (MMDS2) with hyperglycinemia is a severe autosomal recessive disorder characterized by developmental regression in infancy. Affected children have an encephalopathic disease course with seizures, spasticity, loss of head control, and abnormal movement. Additional more variable features include optic atrophy, cardiomyopathy, and leukodystrophy. Laboratory studies show increased serum glycine and lactate. Most patients die in childhood. The disorder represents a form of 'variant' nonketotic hyperglycinemia and is distinct from classic nonketotic hyperglycinemia (NKH, or GCE; {605899}), which is characterized by significantly increased CSF glycine. Several forms of 'variant' NKH, including MMDS2, appear to result from defects of mitochondrial lipoate biosynthesis (summary by Baker et al., 2014).For a general description and a discussion of genetic heterogeneity of multiple mitochondrial dysfunctions syndrome, see MMDS1 (OMIM ).

MULTIPLE MITOCHONDRIAL DYSFUNCTIONS SYNDROME 2 WITH HYPERGLYCINEMIA; MMDS2 Is also known as ;bola3 deficiency

• Autosomal recessive inheritance
• Seizures
• Global developmental delay
• Generalized hypotonia
• Ataxia

SOURCES: ORPHANET OMIM UMLS MONDO DOID

High match MITOCHONDRIAL COMPLEX II DEFICIENCY

Mitochondrial complex II deficiency is an autosomal recessive disorder with a highly variable phenotype. Some patients have multisystem involvement of the brain, heart, muscle, liver, and kidneys resulting in death in infancy, whereas others have only isolated cardiac or muscle involvement with onset in adulthood and normal cognition. Measurement of complex II activity in muscle is the most reliable means of diagnosis; however, there is no clear correlation between residual complex II activity and severity or clinical outcome. In some cases, treatment with riboflavin may have clinical benefit (summary by Jain-Ghai et al., 2013).

MITOCHONDRIAL COMPLEX II DEFICIENCY Is also known as succinate coq reductase deficiency;isolated mitochondrial respiratory chain complex ii deficiency; isolated succinate-coenzyme q reductase deficiency; isolated succinate-ubiquinone reductase deficiency

• Autosomal recessive inheritance
• Seizures
• Global developmental delay
• Short stature
• Generalized hypotonia

SOURCES: GARD UMLS ORPHANET SCTID MONDO OMIM MESH DOID

Medium match CONGENITAL DISORDER OF GLYCOSYLATION, TYPE Im; CDG1M

gene led to a 96 to 98% reduction in DK activity.

CONGENITAL DISORDER OF GLYCOSYLATION, TYPE Im; CDG1M Is also known as cdg im;cdgim, dolichol kinase deficiency, dk1 deficiency;cdg syndrome type im; cdg-im; cdg1m; carbohydrate deficient glycoprotein syndrome type im; congenital disorder of glycosylation type 1m; congenital disorder of glycosylation type im; dolichol kinase deficiency; hypotonia and ichthyosis due to dolichol phosphate deficiency

• Autosomal recessive inheritance
• Seizures
• Global developmental delay
• Short stature
• Generalized hypotonia

SOURCES: ORPHANET UMLS MESH OMIM MONDO SCTID GARD

Medium match MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY (CONGENITAL WITH BRAIN AND EYE ANOMALIES), TYPE A, 4; MDDGA4

MDDGA4 is a severe autosomal recessive muscular dystrophy-dystroglycanopathy with characteristic brain and eye malformations, seizures, and mental retardation. Cardiac involvement in FCMD/MEB occurs in the second decade of life in those who survive. FKTN-related Walker-Warburg syndrome is a more severe manifestation of the disorder, with death usually in the first year of life. These entities are part of a group of similar disorders resulting from defective glycosylation of alpha-dystroglycan (DAG1 ), collectively known as 'dystroglycanopathies' (Godfrey et al., 2007; Muntoni and Voit, 2004; Muntoni et al., 2008).For a general phenotypic description and a discussion of genetic heterogeneity of muscular dystrophy-dystroglycanopathy type A, see MDDGA1 (OMIM ).

MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY (CONGENITAL WITH BRAIN AND EYE ANOMALIES), TYPE A, 4; MDDGA4 Is also known as fukuyama congenital muscular dystrophy;fcmd, walker-warburg syndrome or muscle-eye-brain disease, fktn-related;fcmd; fukuyama congenital muscular dystrophy

• Autosomal recessive inheritance
• Intellectual disability
• Seizures
• Global developmental delay
• Generalized hypotonia

SOURCES: MONDO UMLS SCTID ORPHANET DOID NCIT OMIM

Medium match SHORT STATURE, MICROCEPHALY, AND ENDOCRINE DYSFUNCTION; SSMED

In patients with SSMED, short stature and microcephaly are apparent at birth, and there is progressive postnatal growth failure. Endocrine dysfunction, including hypergonadotropic hypogonadism, multinodular goiter, and diabetes mellitus, is present in affected adults. Progressive ataxia has been reported in some patients, with onset ranging from the second to fifth decade of life. In addition, a few patients have developed tumors, suggesting that there may be a predisposition to tumorigenesis. In contrast to syndromes involving defects in other components of the nonhomologous end-joining (NHEJ) complex (see, e.g., {606593}), no clinically overt immunodeficiency has been observed in SSMED, although laboratory analysis has revealed lymphopenia or borderline leukopenia in some patients (Murray et al., 2015; Bee et al., 2015; de Bruin et al., 2015; Guo et al., 2015).

• Autosomal recessive inheritance
• Global developmental delay
• Short stature
• Hearing impairment
• Microcephaly

SOURCES: UMLS MONDO OMIM

Medium match CHROMOSOME 1p36 DELETION SYNDROME

The constitutional deletion of chromosome 1p36 results in a syndrome with multiple congenital anomalies and mental retardation (Shapira et al., 1997). Monosomy 1p36 is the most common terminal deletion syndrome in humans, occurring in 1 in 5,000 births (Shaffer and Lupski, 2000; Heilstedt et al., 2003).See also neurodevelopmental disorder with or without anomalies of the brain, eye, or heart (NEDBEH ), which shows overlapping features and is caused by heterozygous mutation in the RERE gene (OMIM ) on proximal chromosome 1p36.

CHROMOSOME 1p36 DELETION SYNDROME Is also known as monosomy 1p36 syndrome;del(1)(p36); deletion 1p36; deletion 1pter; monosomy 1p36; monosomy 1pter; subtelomeric 1p36 deletion

• Intellectual disability
• Seizures
• Global developmental delay
• Short stature
• Generalized hypotonia

SOURCES: GARD UMLS ORPHANET MONDO SCTID DOID OMIM NCIT MESH

Medium match DYSKINESIA, FAMILIAL, WITH FACIAL MYOKYMIA; FDFM

Familial dyskinesia and facial myokymia is a rare paroxysmal movement disorder, with childhood or adolescent onset, characterized by paroxysmal choreiform, dystonic, and myoclonic movements involving the limbs (mostly distal upper limbs), neck and/or face, which can progressively increase in both frequency and severity until they become nearly constant. Patients may also present with delayed motor milestones, perioral and periorbital dyskinesias, dysarthria, hypotonia, and weakness.

DYSKINESIA, FAMILIAL, WITH FACIAL MYOKYMIA; FDFM Is also known as ;fdfm

• Autosomal dominant inheritance
• Generalized hypotonia
• Motor delay
• Milia
• Myopathy

SOURCES: MESH UMLS MONDO OMIM ORPHANET GARD